THU0430 RENAL URATE DEPOSITION: SUMMARY OF PUBLISHED EVIDENCE

Abstract

Background:Gout is the most common inflammatory arthropathy in U.S. adults. Although the severity of this debilitating disease is often defined by the presence of tophi in the joints, systemic deposition of urate in major organ systems including the renal parenchyma is not as well established. Urate is primarily cleared through the kidneys and patients with gout often have concomitant renal disease along with other comorbidities such diabetes, coronary artery disease, and hypertension; however, a causal role between these entities has not yet been carefully established. We hypothesize that urate deposits serve as a trigger in the inflammatory nidus to propogate subclinical tissue damage that results in the chronicity of the disease. This could potentially explain its independent role in the development and progression of chronic kidney disease in gout patients.Objectives:To review the published literature for evidence of urate deposition in the renal parenchyma in patients with gout and summarize the histopathology and imaging findings.Methods:PubMed (from 1940 to 2020) was used to identify reports of autopsy, pathology and radiology imaging demonstrating urate deposition within the native renal parenchyma in patients with gout. Key words included: gout nephropathy, chronic urate nephropathy, renal tophi, gouty kidney, autopsy findings in gout, and renal imaging in gout. The reference lists from these publications were also used to identify additional articles. Literature referencing urate nephrolithiasis and renal transplants were excluded from the study.Results:There were 25 articles documenting renal parenchymal urate deposition in gout patients confirmed by autopsy, biopsy and/or radiology imaging in native kidneys. Among the 19 articles examining urate deposition by autopsy and/or biopsy, 100% found urate deposition in the collecting ducts and adjacent medullary interstitium. Based on these findings, the most commonly proposed mechanism for urate deposition is urate crystal precipitation in the collecting ducts with eventual desquamation of the collecting duct walls from inflammation and/or tubular obstruction with subsequent extrusion of crystals into the medullary interstitium. 89% of reports documented inflammatory cells and/or tubulointerstitial fibrosis adjacent to the renal urate deposits. 68% reported cortical thinning or scarring. In addition, 74% of included publications reported renal vascular pathology including arteriosclerosis, glomerosclerosis and nephrosclerosis. There were 6 imaging articles that all reported abnormal renal ultrasound findings with hyperechogenic renal medullas that were attributed to urate deposition.Conclusion:There is a growing body of literature documenting urate deposition in the renal parenchyma in gout patients based on autopsy, pathology and imaging findings. Inflammation and fibrosis adjacent to regions of urate deposition and vascular changes were common. Given the strong association of gout with renal disease, there is a critical need to elucidate the mechanism by which urate impairs the renal tissue. Thus dedicated investigation is key to determine the prevalence and clinical significance of urate deposition in the kidneys of gout patients.References:[1]Nickeleit, V, et al.Nephrol Dial Transplant.(1997) 12:1832-1838.[2]Tchacarski, V, et al.Intl Urol Nephrol.1992; 24(6): 649-655.[3]Modern, FW.Med Clin North Am.1952;21: 941-51.[4]Linnane, JW, et al.Nephron.1981; 29: 216-22[5]Greenbaum, D, et al. Br Med J. 1961 May 27; 1(5238): 1502–1504[6]Bluestone, R, et al.Seminars in Arthr and Rheum.1977;7(2).[7]Brown, J, et al.NEJM.1950; 243: 325-329.[8]Braga, T., et al.Sci Rep.2017; 7: 39884.Disclosure of Interests: :Puja Khanna Grant/research support from: Dyve, Selecta, Sobi, Consultant of: Sobi, Horizon, Brad Marder Employee of: Horizon Therapeutics, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Ada Kumar Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics